ANTISERUM: Dako (M3575). Mouse monoclonal antibody. Clone: 8G7G3/1. Isotype: IgG1k

IMMUNOGEN: recombinant rat TTF-1

INTRODUCTION: Thyroid transcription factor-1 (TTF-1) belongs to a family of homeodomain transcription factors and is selectively expressed in thyroid, lung and diencephalon. TTF-1 has been identified as a transcriptional regulator of thyroid-specific genes and has also been shown to be important in the activation of pulmonary-specific differentiation genes. Clone 8G7G3/1 reacts with rat, mouse and human TTF-1.

REACTIVITY ACCORDING TO MANUFACTURER:
Normal tissues: It demonstrates Clara cells and type II cells of the lung and follicular cells from thyroid. It is unreactive with other tissues examined including prostate, pituitary, testes, adrenal gland, skin, mammary gland, kidney, colon, liver, pancreas, small intestine, brain, and stomach.
Abnormal tissues: It is positive in the majority of pulmonary small cell carcinomas and primary and metastatic pulmonary adenocarcinomas. About 26% of undifferentiated lung carcinomas were negative. Squamous cell carcinomas of the lung are also negative. TTF-1 is positive in most atypical pulmonary carcinoids but not in typical carcinoids. It is also reactive in thyroid papillary carcinomas. Some focal staining can be found in endometrial adenocarcinomas and gastric adenocarcinomas (using a polyclonal antibody to TTF-1).

STAINING PROCEDURE ACCORDING TO MANUFACTURER:
Formalin-fixed, paraffin-embedded tissues: LSAB+/PO at 1/200 or LSAB2/PO at 1/50. Heat antigen retrieval is mandatory (40 minute heating protocol).
Frozen sections: It is also possible with this antibody.

WORKING DILUTION: 1/10000. Pretreatment with steamer (EDTA, pH 8.0) 40 minutes.

METHOD: ENVISION+/PO, 90 min., RT

CELLS/TISSUES STAINED (canine tissues unless specified):
The staining is nuclear.
Lung: Numerous epithelial cells of bronchioles. Large airways are mostly unreactive. Numerous alveolar cells with plump nuclei are also positive. No apparent staining of endothelium or lymphoid cells or stroma.
Pulmonary carcinoma: Intense staining of neoplastic cells.
Thyroid: Nuclear staining of some follicular cells and probably some C-cells. Parathyroid gland is negative. Thyroid neoplasia: The majority of follicular tumors are positive and about 45-50% of C-cell tumors. TTF-1 is slightly less sensitive than thyroglobulin for follicular tumors and much less sensitive than calcitonin for C-cell tumors.

REFERENCES:

Anderson SS, Langel DJ, Gown AM, Prasad A, Savera A, Zarbo RJ (1998) Thyroid transcription factor-1 (TTF-1) is a more sensitive lung carcinoma marker than surfactant ApoA1. Lab Invest 78:171A

Bejarano PA, Baughman RP, Biddinger PW, Miller MA, Fenoglio-Preiser C, Al-kafaji B, Di Lauro R, Whitsett JA (1996) Surfactant proteins and thyroid transcription factor-1 in pulmonary and breast carcinomas. Mod Pathol 9:445-

Bohinski RJ, Di Lauro R, Whitsett JA (1994) The lung-specific surfactant protein B gene promoter is a target for thyroid transcription fator-1 and hepatocyte nuclear factor-3, indicating common factors for organ-specific gene expression along the foregut axis. Mol Cell Biol 14:5671-5681

Bohinski RJ, Bejarano PA, Balko G, Warnick RE Whitsett JA (1998) Determination of lung as the primary site of cerebral metastatic adenocarcinomas using monoclonal antibody to thyroid transcription factor-1. J Neurol Oncol 40:227-231.

Folpe AL, hansen D, Gown AM, Schmidt RA (1998) Expression of thyroid transcription factor-1 (TTF-1) is common in pulmonary atypical carcinoids and small cell carcinomas, but not typical carcinoids. Lab Invest 78:174A

Harlamert HA, Mira J, Yassin R, Bejarano PA, Baughman R, Miller MA, Whitsett J (1997) Distinguishing primary lung adenocarcinomas from metastatic breast adenocarcinomas in cytology specimens using TTF-1 and cytokeratins 7 and 20. Mod Pathol 10:A185-

Holzinger A, Dingle S, Bejarano PA, Miller M-A, Weaver TE, Di Lauro R, Whitsett JA (1996)Monoclonal antibody to thyroid transcription factor-1: Production, characterization and usefulness in tumor diagnosis. Hybridoma 15:49-53

Khoor A, Whitsett JA, Stahlman MT, Stephenson M, Olson SJ, Cagle PT (1999) Utility of surfactant protein B precursor and thyroid transcription factor 1in differentiating adenocarcinoma of the lung from malignant mesothelioma. Hum Pathol 30:695-700

Lazzaro D, Price M, De Felice M, Di Lauro R (1991) The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the fetal brain. Development 113:1093-1104

Pelosi G, Fraggetta F, Pasini F, maisonneuve P, Sonzogni A et al (2001) Immunoreactivity of thyroid transcription factor-1 in stage I non-small cell carcinomas of the lung. Am J Surg Pathol 25:363-372

Ramos-Vara JA, Miller MA, Johnson GC, Pace LW (2002) Immunohistochemical detection of thyroid transcription factor-1, thyroglobulin, and calcitonin in canine normal, hyperplastic, and neoplastic thyroid gland. Vet Pathol 39:480-487

Stah;aman MT, Gray ME, Whitsett JA (1996) Expression of thyroid transcription factor-1 in C cells and parathyroid cells. J Histochem Cytochem 44:673-678

Suzuki K, Kobayashi Y, Katoh R, Kohn LD, Kawaoi A (1998) identification of thyroid transcription factor-1 in C cells and parathyroid cells. Endocrinology 139:3014-3017

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IMAGES

Thyroid, Dog. Fig. 1. Thyroid follicular adenoma. Nuclear staining for TTf-1 in most of follicular epithelial cells. 2. Thyroid follicular carcinoma. Fig. 3. Detail of nuclear stsining for TTF-1 in thyroid follicular carcinoma. Fig. 4. Metastatic C-cell carcinoma to a lymph node. Lymphoid tissue is nonreactive. Immunoperoxidase-DAB for thyroid transcription factor-1 (TTF-1).